Referenced in: none

Automatically associated channels: Kir2.2 , Kir3.2 , Slo1

Title: Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA.

Authors: Claire L Padgett, Arnaud L Lalive, Kelly R Tan, Miho Terunuma, Michaelanne B Munoz, Menelas N Pangalos, José Martínez-Hernández, Masahiko Watanabe, Stephen J Moss, Rafael Lujan, Christian Lüscher, Paul A Slesinger

Journal, date & volume: Neuron, 2012 Mar 8 , 73, 978-89

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22405207

Abstract
Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3)) channels, however, are poorly understood. Here, we show that 1 day after methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen-activated GABA(B)R-GIRK currents were significantly depressed in VTA GABA neurons and remained depressed for 7 days. Presynaptic inhibition mediated by GABA(B)Rs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABA(B1) and GIRK2, which occurred coincident with dephosphorylation of serine 783 (S783) in GABA(B2), a site implicated in regulating GABA(B)R surface expression. Inhibition of protein phosphatases recovered GABA(B)R-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABA(B)R signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system.